This work reports the antiproliferative activity of seco-oxacassanes 1–3, isolated from Acacia schaffneri, against human colon (HT-29), lung (A-549), and melanoma (UACC-62) cancer cell lines, as well as against their non-malignant counterparts CCD-841 CoN, MRC-5, and VH-10, respectively, using the sulforhodamine B test. While compounds 1 and 3 were inactive, 2 presented strong activity with IC50 values between 0.12 and 0.92 μg mL–1. The cytotoxicity mechanisms of 2 were investigated by cell cycle analysis and through DNA repair pathways, indicating that the compound is capable of arresting the cell cycle in the G0/G1 phase. This effect might be generated through damage to DNA by alkylation. In addition, compound 2 was able to decrease HT-29 migration.
JemalA, BrayF, CenterMM, FerlayJ, WardE, FormanD. (2011) Global cancer statistics. CA: Cancer Journal Clinicians, 61, 69–90.
2.
SiegelR, MaJ, ZouZ, JemalA. (2014) Cancer statistics. CA: Cancer Journal Clinicians, 64, 9–29.
3.
WesthoffM-A, BrühlO, NonnenmacherL, Karpel-MasslerG, DabatinK-M. (2014) Killing me softly—Future challenges in apoptosis research. International Journal of Molecular Sciences, 15, 3746–3767.
4.
VilanovaC, Díaz-OltraS, MurgaJ, FalomirE, CardaM, Redondo-HorcajoM, DíazJF, BarasoainI, MarcoJA. (2014) Design and synthesis of pironetin analogue/colchicine hybrids and study of their cytotoxic activity and mechanisms of interaction with tubulin. Journal of Medicinal Chemistry, 57, 10391–10403.
5.
BelmontF, JourdanM, DemeunynckM, ConstantJ-F, GarciaJ, LhommeJ, CarezD, CroisyA. (1999) Abasic site recognition in DNA as a new strategy to potentiate the action of anticancer alkylating drugs?Journal of Medicinal Chemistry, 42, 5153–5159.
6.
PallisAG, KaramouzisMV. (2010) DNA repair pathways and their implication in cancer treatment. Cancer Metastasis Review, 29, 677–685.
7.
ChristmannM, TomicicMT, RoosWP, KainaB. (2003) Mechanisms of human DNA repair: an update. Toxicology, 193, 3–34.
8.
HelledayT, PetermannE, LundinC, HodgsonB, SharmaRA. (2008) DNA repair pathways as target for cancer therapy. Nature Review Cancer, 8, 193–204.
9.
Calderón-MontañoJM, Burgos-MorónE, OrtaML, López-LázaroM. (2014) Effect of DNA repair deficiencies on the cytotoxicity of drugs used in cancer therapy - A review. Current Medicinal Chemistry, 21, 3419–3454.
10.
BarniMV, CarliniMJ, CafferataEG, PuricelliL, MorenoS. (2012) Carnosic acid inhibits the proliferation and migration capacity of human colorectal cancer cells. Oncology Reports, 27, 1041–1048.
11.
Manríquez-TorresJJ, Torres-ValenciaJM, Gómez-HurtadoMA, MotilvaV, García-MauriñoS, ÁvilaJ, TaleroE, Cerda-García-RojasCM, Joseph-NathanP. (2011) Absolute configuration of 7,8-seco–7,8-oxacassane diterpenoids from Acacia schaffneri. Journal of Natural Products, 74, 1946–1951.
12.
Manríquez-TorresJJ, Torres-ValenciaJM, Velázquez-JiménezR, Valdez-CalderónA, Alvarado-RodríguezJG, Cerda-García-RojasCM, Joseph-NathanP. (2013) A macrocyclic dimeric diterpene with a C2 symmetry axis. Organic Letters, 15, 4658–4661.
13.
JohanssonF, LagerqvistA, FilippiS, PalittiF, ErixonK, HelledayT, JenssenD. (2006) Caffeine delays replication fork progression and enhances UV-induced homologous recombination in Chinese hamster cell lines. DNA Repair, 5, 1449–1458.
14.
LoizouJI, El-KhamisySF, ZlatanouA, MooreDJ, ChanDW, QuinJ, SarnoS, MeggioF, PinnaLA, CaldecottKW. (2004) The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks. Cell, 117, 17–28.
15.
ScottiMT, FernandesMB, FerreiraMJP, EmerencianoVP. (2007) Quantitative structure-activity relationship of sesquiterpene lactones with cytotoxic activity. Bioorganic & Medicinal Chemistry, 15, 2927–2934.
16.
SkehanP, StorengR, ScudieroD, MonksA, McMahonJ, VisticaD, WarrenJT, BokeschH, KenneyS, BoydMR. (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. Journal of the National Cancer Institute, 82, 1107–1112.
17.
SundarrajS, ThangamR, SreevaniV, KaveriK, GunasekaranP, AchiramanS, KannanS. (2012) γ-Sitosterol from Acacia nilotica L. induces G2/M cell cycle arrest and apoptosis through c-Myc suppression in MCF-7 and A549 cells. Journal of Ethnopharmacology, 141, 803–809.
18.
LeeH, KangC, JungE-s, KimJ-S, KimE. (2011) Antimetastatic activity of polyphenol-rich extract of Ecklonia cava through the inhibition of the Akt pathway in A549 human lung cancer cells. Food Chemistry, 127, 1229–1236.
